Updated Definitions of Healthy ALT Ranges

Prati et al. • Ann Intern Med

Key Finding

Truly healthy ALT upper limits are 30 U/L for men and 19 U/L for women — far below standard lab ranges.

Original title: “Updated definitions of healthy ranges for serum alanine aminotransferase levels”

Plain English Summary

Landmark study analyzing 6,835 healthy blood donors to establish truly healthy ALT upper limits. Found conventional ranges included many with subclinical liver disease.

In-Depth Analysis

Background

Dr. Daniele Prati and colleagues from the AASLD Blood Donor Study published this landmark study in Annals of Internal Medicine (PMID: 12093239), establishing truly healthy ALT reference ranges from carefully screened blood donors.

Study Design

Design: Cross-sectional study of healthy blood donors Population: 6,835 first-time blood donors in Northern Italy Exclusions: Rigorous screening for all known causes of liver disease

•Hepatitis B and C
•Excessive alcohol (>20 g/day women, >30 g/day men)
•Diabetes or metabolic syndrome
•Medications affecting liver
•Obesity (BMI >25) Analysis: Distribution of ALT in truly healthy population

Key Findings

Proposed healthy ALT upper limits:

Sex	Proposed ULN	Traditional ULN
Men	30 U/L	40-65 U/L
Women	19 U/L	35-50 U/L

Distribution findings:

•95th percentile was much lower than traditional lab cutoffs
•Traditional ranges included subclinically unhealthy individuals
•Using lower cutoffs identified more NAFLD, hepatitis C cases

Key insight: Traditional "normal" ALT ranges were derived from unscreened populations containing people with subclinical liver disease.

Mechanistic Insights

ALT elevates when hepatocytes are damaged:

•Even mild steatosis raises ALT
•Conventional ranges miss 50%+ of NAFLD cases
•Small elevations within "normal" predict mortality

Clinical Implications

Using lower thresholds (30 M, 19 F):

•Identifies more patients with early liver disease
•Prompts earlier evaluation and intervention
•Better predicts metabolic dysfunction

Metabolic Health Perspective

For metabolic optimization, truly healthy ALT levels are: Men <25 U/L, Women <17 U/L. Values approaching conventional cutoffs may indicate early metabolic liver dysfunction worth investigating.